title: Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg(+) and HBeAg(-) patients.
abstract: OBJECTIVE
  To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.
  
  
  METHODS
  Sixty-four patients with chronic hepatitis, 65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study. HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing. Viral load was measured by real-time polymerase chain reaction.
  
  
  RESULTS
  Of 179 patients, 108 (60.3%) were HBeAg(-) and 86 (79.6%) of these HBeAg(-) patients had been seroconverted. The A1896 mutation was not found in HBeAg(+) patients, however, this mutation was detected in 70.7% of HBeAg(-) patients. This mutation was frequently found when HBeAg was not expressed (87.7%), compared to that found in HBeAg seroconverted patients (65.1%). The A1899 mutation was also more prevalent in HBeAg(-) than in HBeAg(+) patients (P = 0.004). The T1762/A1764 mutation was frequently found in both HBeAg(+) and HBeAg(-) patients, however, the prevalence of this mutation did not significantly differ among the two groups (P = 0.054). In HBeAg(+) patients, the T1762/A1764 mutation was correlated with lower HBV DNA (P < 0.001). The A1899 mutation did not correlate with HBV DNA (P = 0.609). In HBeAg(-) patients, the T1762/A1764 mutation alone was not correlated with HBV DNA (P = 0.095), however, the presence of either the T1762/A1764 or A1896 mutations was associated with increased HBV DNA (P < 0.001).
  
  
  CONCLUSIONS
  The percentage of HBeAg(-) patients is high in Indonesia, and most of the HBeAg(-) patients had been seroconverted. The A1896 mutation was most likely the major cause of HBeAg loss. The T1762/A1764 mutation alone was associated with lower viral loads in HBeAg(+) patients, but not in HBeAg(-) patients.
authors.affiliation: Molecular Epidemiology Division, Mochtar Riady Institute for Nanotechnology, Universitas Pelita Harapan, Lippo Karawaci, Tangerang, 15810, Indonesia. autama@mrinstitute.org
authors.forename: Andi
authors.initials: A
authors.lastname: Utama
authors.forename: Marlinang Diarta
authors.initials: MD
authors.lastname: Siburian
authors.forename: Sigit
authors.initials: S
authors.lastname: Purwantomo
authors.forename: Mariana Destila Bayu
authors.initials: MD
authors.lastname: Intan
authors.forename: Tri Shinta
authors.initials: TS
authors.lastname: Kurniasih
authors.forename: Rino Alvani
authors.initials: RA
authors.lastname: Gani
authors.forename: Wenny Astuti
authors.initials: WA
authors.lastname: Achwan
authors.lastname: Arnelis
authors.forename: Syafruddin A R
authors.initials: SA
authors.lastname: Lelosutan
authors.forename: Benyamin
authors.initials: B
authors.lastname: Lukito
authors.forename: Tantoro
authors.initials: T
authors.lastname: Harmono
authors.forename: Nasrul
authors.initials: N
authors.lastname: Zubir
authors.lastname: Julius
authors.forename: Soewignjo
authors.initials: S
authors.lastname: Soemohardjo
authors.forename: Laurentius Adrianus
authors.initials: LA
authors.lastname: Lesmana
authors.forename: Ali
authors.initials: A
authors.lastname: Sulaiman
authors.forename: Susan
authors.initials: S
authors.lastname: Tai
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000378:metabolism; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase